Document Detail


D-cycloserine administered directly to infralimbic medial prefrontal cortex enhances extinction memory in sucrose-seeking animals.
MedLine Citation:
PMID:  23159319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
d-Cycloserine (DCS), a co-agonist at the N-methyl-D-aspartate (NMDA) receptor, has proven to be an effective adjunct to cognitive behavioral therapies that utilize extinction. This pharmacological-based enhancement of extinction memory has been primarily demonstrated in neuropsychiatric disorders characterized by pathological fear (e.g. posttraumatic stress disorder and various phobias). More recently, there has been an interest in applying such a strategy in the disorders of appetitive learning (e.g. substance abuse and other addictions), but these studies have generated mixed results. Here we first examined whether extinction memory encoding in a sucrose self-administration model is dependent on NMDA receptors. The NMDA antagonist (±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (5mg/kg, i.p.) administered 2h prior to the first extinction training session effectively inhibited extinction memory recall 24h later, without affecting the expression of the conditioned sucrose-seeking response while the drug was on board. This profile of effects suggests a specific effect on extinction memory consolidation. Next, we sought to enhance extinction memory using the co-agonist DCS (10 μg/side) by infusion directly into infralimbic medial prefrontal cortex, a brain site implicated in extinction memory recall in conditioned fear models. Indeed, infusion of DCS immediately after the first extinction training session effectively enhanced extinction memory recall 24h later. Collectively, these data suggest that the neurobiological mechanisms and the neurocircuitry mediating extinction memory are similar regardless of the valence (aversive or appetitive) of the conditioned behavior, and that similar pharmacological strategies for treatment may be applied to neuropsychiatric disorders characterized by a failure to inhibit pathological emotional memories.
Authors:
J Peters; T J De Vries
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Neuroscience     Volume:  230     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-14     Completed Date:  2013-07-01     Revised Date:  2014-02-07    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Conditioning, Operant / drug effects
Cycloserine / pharmacology*
Excitatory Amino Acid Agonists / pharmacology*
Excitatory Amino Acid Antagonists / pharmacology
Extinction, Psychological / drug effects*
Food Preferences / drug effects*
Male
Piperazines / pharmacology
Prefrontal Cortex / drug effects*
Rats
Rats, Wistar
Self Administration
Sucrose / administration & dosage*
Sweetening Agents / administration & dosage*
Time Factors
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Piperazines; 0/Sweetening Agents; 100828-16-8/3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; 57-50-1/Sucrose; 95IK5KI84Z/Cycloserine
Comments/Corrections
Erratum In:
Neuroscience. 2014 Jan 3;256:478

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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